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https://www.readbyqxmd.com/read/28933662/deficiency-of-serotonin-in-raphe-neurons-and-altered-behavioral-responses-in-tryptophan-hydroxylase-2-knockout-medaka-oryzias-latipes
#1
Satoshi Ansai, Hiroshi Hosokawa, Shingo Maegawa, Kiyoshi Naruse, Youhei Washio, Kenji Sato, Masato Kinoshita
Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(Δ13/Δ13)) lacked the ability to synthesize 5-HT in the raphe neurons...
September 21, 2017: Zebrafish
https://www.readbyqxmd.com/read/28902619/a-case-control-association-study-of-12-candidate-genes-and-attempted-suicide-in-french-adolescents
#2
Bojan Mirkovic, David Cohen, Claudine Laurent, Malaika Lasfar, Christophe Marguet, Prsicille Gerardin
Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified...
September 13, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28888667/preimmunization-with-a-heat-killed-preparation-of-mycobacterium-vaccae-enhances-fear-extinction-in-the-fear-potentiated-startle-paradigm
#3
James H Fox, James E Hassell, Philip H Siebler, Mathew R Arnold, Andrew K Lamb, David G Smith, Heidi E W Day, Tessa M Smith, Emma M Simmerman, Alexander A Outzen, Kaley S Holmes, Christopher J Brazell, Christopher A Lowry
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience...
September 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28866660/generation-of-tryptophan-hydroxylase-2-gene-knockout-pigs-by-crispr-cas9-mediated-gene-targeting
#4
Ze Li, Hai-Yuan Yang, Ying Wang, Man-Ling Zhang, Xiao-Rui Liu, Qiang Xiong, Li-Ning Zhang, Yong Jin, Li-Sha Mou, Yan Liu, Rong-Feng Li, Yi Rao, Yi-Fan Dai
Unbalanced brain serotonin (5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2 (TPH2). In the present study, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at 38...
September 3, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28856708/degeneration-of-serotonin-neurons-triggers-spasticity-in-amyotrophic-lateral-sclerosis
#5
Hajer El Oussini, Jelena Scekic-Zahirovic, Pauline Vercruysse, Christine Marques, Sylvie Dirrig-Grosch, Stéphane Dieterlé, Gina Picchiarelli, Jérôme Sinniger, Caroline Rouaux, Luc Dupuis
OBJECTIVE: Spasticity occurs in a wide range of neurological diseases, including neurodegenerative diseases, after trauma or after stroke and is characterized by increased reflexes leading to muscle hypertonia. Spasticity is a painful symptom and can severely restrict everyday life, but might also participate in maintaining a low level of motor function in severely impaired patients. Constitutive activity of the serotonin receptors 5-HT2B/C is required for the development of spasticity after spinal cord injury or during amyotrophic lateral sclerosis (ALS)...
August 30, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28775068/active-sleep-unmasks-apnea-and-delayed-arousal-in-infant-rat-pups-lacking-central-serotonin
#6
Jacob O Young, Aron M Geurts, Matthew Robert Hodges, Kevin J Cummings
Sudden Infant Death Syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28769763/development-of-serotonergic-fibers-in-the-post-natal-mouse-brain
#7
Giacomo Maddaloni, Alice Bertero, Marta Pratelli, Noemi Barsotti, Annemarie Boonstra, Andrea Giorgi, Sara Migliarini, Massimo Pasqualetti
Serotonin (5-HT)-synthetizing neurons, which are confined in the raphe nuclei of the rhombencephalon, provide a pervasive innervation of the central nervous system (CNS) and are involved in the modulation of a plethora of functions in both developing and adult brain. Classical studies have described the post-natal development of serotonergic axons as a linear process of terminal field innervation. However, technical limitations have hampered a fine morphological characterization. With the advent of genetic mouse models, the possibility to label specific neuronal populations allowed the rigorous measurement of their axonal morphological features as well as their developmental dynamics...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28751217/human-placenta-expresses-both-peripheral-and-neuronal-isoform-of-tryptophan-hydroxylase
#8
Laetitia Laurent, Kathy Deroy, Joey St-Pierre, Francine Côté, J Thomas Sanderson, Cathy Vaillancourt
The role of placental serotonin has been an active topic of research notably because of its crucial role in brain development. However, which cell types synthesize serotonin in human placenta remains unknown. Moreover, it is not known if the two tryptophan hydroxylase isoforms (TPH1 and TPH2), the rate-limiting enzymes in serotonin biosynthesis, are expressed in placenta. Human placentas were obtained in first trimester or at term, and trophoblast cells were isolated and purified using a magnetic cell sorter and placed in primary culture...
September 2017: Biochimie
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#9
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#10
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28706142/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#11
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687505/xiaochaihutang-attenuates-depressive-anxiety-like-behaviors-of-social-isolation-reared-mice-by-regulating-monoaminergic-system-neurogenesis-and-bdnf-expression
#12
Jie Ma, Fang Wang, Jingyu Yang, Yingxu Dong, Guangyue Su, Kuo Zhang, Xing Pan, Ping Ma, Tingshuo Zhou, Chunfu Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression...
July 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28650979/expression-of-cerebral-serotonin-related-to-anxiety-like-behaviors-in-c57bl-6-offspring-induced-by-repeated-subcutaneous-prenatal-exposure-to-low-dose-lipopolysaccharide
#13
Pei-Tan Hsueh, Hsuan-Han Wang, Chiu-Lin Liu, Wei-Fen Ni, Ya-Lei Chen, Jong-Kang Liu
Prenatal exposure to lipopolysaccharide (LPS), which likely occurs due to infection or contact with environmental allergens during pregnancy, is a proposed risk factor that induces anxiety- and autism spectrum disorder-like behaviors in offspring. However, the molecular and behavioral changes in offspring after maternal immune activation have not been completely identified. We hypothesized that a subcutaneous injection of LPS in a pregnant mouse would induce changes in cerebral serotonin (5-HT) in parallel to the appearance of anxiety-like behaviors in the dam's offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28630479/attention-cognitive-control-and-motivation-in-adhd-linking-event-related-brain-potentials-and-dna-methylation-patterns-in-boys-at-early-school-age
#14
Hartmut Heinrich, Juliane Grunitz, Valeska Stonawski, Stefan Frey, Simone Wahl, Björn Albrecht, Tamme W Goecke, Matthias W Beckmann, Johannes Kornhuber, Peter A Fasching, Gunther H Moll, Anna Eichler
In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28590957/genetic-moderation-of-cocaine-subjective-effects-by-variation-in-the-tph1-tph2-and-slc6a4-serotonin-genes
#15
Michelle A Patriquin, Sara C Hamon, Mark J Harding, Ellen M Nielsen, Thomas F Newton, Richard De La Garza, David A Nielsen
OBJECTIVE: This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine. METHODS: Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion...
October 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28579486/no-effect-of-c1473g-polymorphism-in-the-tryptophan-hydroxylase-2-gene-on-the-response-of-the-brain-serotonin-system-to-chronic-fluoxetine-treatment-in-mice
#16
Ekaterina Y Bazhenova, Nadezhda A Sinyakova, Elizabeth A Kulikova, Irina A Kazarinova, Daria V Bazovkina, Raul R Gainetdinov, Alexander V Kulikov
Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block serotonin transporter (SERT) and increase serotonin (5-HT) level in the synaptic cleft. The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level. The G allele of C1473G polymorphism in Tph2 gene decreases enzyme activity by half in mouse brain. Here we studied effect of C1473G polymorphism on the reaction of brain 5-HT system to chronic fluoxetine treatment (120mg/l in drinking water, for 3 weeks) in adult males of the congenic B6-1473C and B6-1473G mouse lines with high and low enzyme activity, respectively...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28555406/investigation-of-previously-implicated-genetic-variants-in-chronic-tic-disorders-a-transmission-disequilibrium-test-approach
#17
Mohamed Abdulkadir, Douglas Londono, Derek Gordon, Thomas V Fernandez, Lawrence W Brown, Keun-Ah Cheon, Barbara J Coffey, Lonneke Elzerman, Carolin Fremer, Odette Fründt, Blanca Garcia-Delgar, Donald L Gilbert, Dorothy E Grice, Tammy Hedderly, Isobel Heyman, Hyun Ju Hong, Chaim Huyser, Laura Ibanez-Gomez, Ewgeni Jakubovski, Young Key Kim, Young Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett Leventhal, Andrea G Ludolph, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Kirsten Müller-Vahl, Alexander Münchau, Tara L Murphy, Kerstin J Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Jennifer Tübing, Els van den Ban, Frank Visscher, Sina Wanderer, Martin Woods, Samuel H Zinner, Robert A King, Jay A Tischfield, Gary A Heiman, Pieter J Hoekstra, Andrea Dietrich
Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort...
May 29, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28537235/-serotonergic-genes-in-the-development-of-anxiety-depression-like-state-and-pathology-of-aggressive-behavior-in-male-mice-rna-seq-data
#18
N N Kudryavtseva, D A Smagin, I L Kovalenko, A G Galyamina, G B Vishnivetskaya, V N Babenko, Yu L Orlov
In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#19
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28464229/functional-characterization-of-the-neuron-restrictive-silencer-element-in-the-human-tryptophan-hydroxylase-2-gene-expression
#20
Yukino Nawa, Hanae Kaneko, Masayuki Oda, Masaaki Tsubonoya, Tomoko Hiroi, Maria Teresa Gentile, Luca Colucci-D'Amato, Ryoya Takahashi, Hiroaki Matsui
Tryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 NRSE (neuron-restrictive silencer element) functions as a negative regulator dependent on NRSF (neuron-restrictive silencer factor) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons. Quantitative real-time RT-PCR analysis revealed the expression of serotonergic marker genes (Mash1, Nkx2...
May 2, 2017: Journal of Neurochemistry
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